172 research outputs found

    A Framework of Contextualized Teaching and Learning: Assisting Developmental Education Instructors

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    Contextualization in Developmental Education (DE) classrooms is often recommended but underutilized. The Framework of Contextualized Teaching and Learning is based upon existing research and theory in the field. It will help instructors create contextualized lessons and provide researchers a framework for categorizing studies on contextualization

    Tolerance induced via TLR2 and TLR4 in human dendritic cells: role of IRAK-1

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    <p>Abstract</p> <p>Background</p> <p>While dendritic cells (DCs) can induce tolerance in T cells, little is known about tolerance induction in DCs themselves. We have analysed tolerance induced in human <it>in-vitro </it>generated DCs by repeated stimulation with ligands for TLR4 and TLR2.</p> <p>Results</p> <p>DCs stimulated with the TLR4 ligand LPS did show a rapid and pronounced expression of TNF mRNA and protein. When DCs were pre-cultured for 2 days with 5 ng LPS/ml then the subsequent response to stimulation with a high dose of LPS (500 ng/ml) was strongly reduced for both TNF mRNA and protein. At the promoter level there was a reduced transactivation by the -1173 bp TNF promoter and by a construct with a tetrameric NF-ÎșB motif. Within the signalling cascade leading to NF-ÎșB activation we found an ablation of the IRAK-1 adaptor protein in LPS-tolerant DCs. Pre-culture of DCs with the TLR2 ligand Pam3Cys also led to tolerance with respect to TNF gene expression and IRAK-1 protein was ablated in such tolerant cells as well, while IRAK-4 protein levels were unchanged.</p> <p>Conclusion</p> <p>These data show that TLR-ligands can render DCs tolerant with respect to TNF gene expression by a mechanism that likely involves blockade of signal transduction at the level of IRAK-1.</p

    SHERPA Position Paper - Empowering rural areas in multi-level governance processes

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    This SHERPA Position Paper builds on the contributions of all 41 SHERPA Multi-Actor Platforms (MAPs) involved in the fourth (and final) cycle of the SHERPA project. During this final cycle, MAPs were asked to reflect on how to empower regional and local institutions and actors in multi-level decision-making processes in rural areas, and propose recommendations for policy and future research on this topic. Each MAP discussed the elements they found most relevant for their geographical area in relation to multi-level governance in rural areas, and used this as their MAP input for the development of this Position Paper. More information on this topic from each individual MAP can be found in the MAP Fiches

    Helicobacter pylori and cancer among adults in Uganda

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    Data from Africa on infection with Helicobacter pylori (H. pylori) are sparse. Therefore, as part of an epidemiological study of cancer in Uganda, we investigated the prevalence and determinants of antibodies against H. pylori among 854 people with different cancer types and benign tumours. Patients were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against H. pylori. In all patients combined, excluding those with stomach cancer (which has been associated with H. pylori infection), the prevalence of antibodies was 87% (723/833) overall, but declined with increasing age (p = 0.02) and was lower among people who were HIV seropositive compared to seronegative (p <0.001). Otherwise, there were few consistent epidemiological associations. Among those with stomach cancer, 18/21 (86%) had anti-H. pylori antibodies (odds ratio 0.8, 95% confidence intervals 0.2–2.9, p = 0.7; estimated using all other patients as controls, with adjustment for age, sex and HIV serostatus). No other cancer site or type was significantly associated with anti-H. pylori antibodies. The prevalence of H. pylori reported here is broadly in accord with results from other developing countries, although the determinants of infection and its' role in the aetiology of gastric cancer in Uganda remain unclear

    Policies and practices of SHEA Research Network hospitals during the COVID-19 pandemic

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    To understand hospital policies and practices as the COVID-19 pandemic accelerated, the Society for Healthcare Epidemiology of America (SHEA) conducted a survey through the SHEA Research Network (SRN). The survey assessed policies and practices around the optimization of personal protection equipment (PPE), testing, healthcare personnel policies, visitors of COVID-19 patients in relation to procedures, and types of patients. Overall, 69 individual healthcare facilities responded in the United States and internationally, for a 73% response rate

    The PPAR-Îł agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys

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    <p>Abstract</p> <p>Background</p> <p>Activation of the peroxisome proliferator-activated receptor gamma (PPAR-Îł) has been proposed as a possible neuroprotective strategy to slow down the progression of early Parkinson's disease (PD). Here we report preclinical data on the use of the PPAR-Îł agonist pioglitazone (Actos<sup>Âź</sup>; Takeda Pharmaceuticals Ltd.) in a paradigm resembling early PD in nonhuman primates.</p> <p>Methods</p> <p>Rhesus monkeys that were trained to perform a battery of behavioral tests received a single intracarotid arterial injection of 20 ml of saline containing 3 mg of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Twenty-four hours later the monkeys were assessed using a clinical rating scale, matched accordingly to disability, randomly assigned to one of three groups [placebo (n = 5), 2.5 (n = 6) or 5 (n = 5) mg/kg of pioglitazone] and their treatments started. Three months after daily oral dosing, the animals were necropsied.</p> <p>Results</p> <p>We observed significant improvements in clinical rating score (<it>P </it>= 0.02) in the animals treated with 5 mg/kg compared to placebo. Behavioral recovery was associated with preservation of nigrostriatal dopaminergic markers, observed as higher tyrosine hydroxylase (TH) putaminal optical density (<it>P </it>= 0.011), higher stereological cell counts of TH-ir (<it>P </it>= 0.02) and vesicular monoamine transporter-2 (VMAT-2)-ir nigral neurons (<it>P </it>= 0.006). Stereological cell counts of Nissl stained nigral neurons confirmed neuroprotection (<it>P </it>= 0.017). Pioglitazone-treated monkeys also showed a dose-dependent modulation of CD68-ir inflammatory cells, that was significantly decreased for 5 mg/kg treated animals compared to placebo (<it>P </it>= 0.018). A separate experiment to assess CSF penetration of pioglitazone revealed that 5 mg/kg p.o. induced consistently higher levels than 2.5 mg/kg and 7.5 mg/kg. p.o.</p> <p>Conclusions</p> <p>Our results indicate that oral administration of pioglitazone is neuroprotective when administered early after inducing a parkinsonian syndrome in rhesus monkeys and supports the concept that PPAR-Îł is a viable target against neurodegeneration.</p

    Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

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    The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

    Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

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    Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≄ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk
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